Interdisciplinary Initiatives Program Round 12 - 2024
Project Investigators:
Longzhi Tan, Neurobiology
Hawa Racine Thiam, Bioengineering and Microbiology & Immunology
Abstract:
Our proposal explores the intriguing concept that the 3D organization of our DNA in the cell nucleus goes beyond controlling gene activity: as a two-meter-long biopolymer tightly packed in a multi-micron-sized nucleus, DNA can also directly control the cell’s mechanical properties (shape, volume, stiffness…) and thus functions. By rapidly altering DNA organization before changes in gene activity could take place, we aim to understand how the 3D structure of our genome affects the nucleus’s shape and stiffness, therefore impacting critical cell functions like division, movement, and the ability to kill of pathogens. Focusing on the innate immune system, we will combine advanced technologies in DNA sequencing and in microscopy to measure 3D DNA structure and mechanical properties of the same immune cell, to uncover how biophysical properties of DNA controls cellular functions and disease. By bridging biology and engineering, and connecting genomics (Tan lab), immunology (Thiam lab), and biophysics (both labs), this work will provide new insights into designing cell therapy and disease treatment without altering gene expression, pioneering the understanding of cellular mechanics driven by DNA organization.
